tbuckley/cabot-search huggingface dataset:
Abstract 14480: Importance of the Characteristics of Aortic Valve Calcification for Identifying Patients at a High Risk for Permanent Pacemaker Implantation After Different Types of Transcatheter Aortic Valve Replacement
Authors: Zhifeng Dong, Alberto Ardura-Fabregat, David X Zhao, Li Zhou, Mario J Garcia, Min Pu
Journal: Circulation (2022)

Background: Aortic valve calcification is a known risk factor for permanent pacemaker implantation (PPMI) following transcatheter aortic valve replacement (TAVR). However, the impact of characteristics of the calcium deposit on the aortic valve and annulus on post-TAVR PPMI has not been well defined. Hypothesis: Analysis of the characteristics of aortic valve calcification and its interactions with different types of TAVR could identify patients at a high risk for PPMI. Methods: This single-center retrospective study included 352 patients treated with TAVR for severe symptomatic aortic stenosis. One hundred ninety-three patients received self-expanding (SE) valves and 159 patients received balloon-expandable (BE) valves. Aortic valve calcification was evaluated using multi-slice computed tomography (MSCT) and 3mensio™ software prior to the TAVR. Total calcium volume (TCV) in the aortic valve was measured in the space ±10 mm of the aortic annulus. In addition, the largest calcium nodule diameter (LCND) was measured at the non-coronary cusp - right coronary cusp commissure, which is anatomically adjacent to the His bundle. TCV and LCND were compared among patients who required PPMI vs. those who did not. Results: PPMI was required post-TAVR in 69 subjects (25.9% in SE and 11.9% in BE, p&lt;0.05). TCV was not associated with an increased risk of post-TAVR PPMI. However, the risk of PPMI increased incrementally in patients who received SE valves from LCND measured 1mm, 1-5 mm, 5-10 mm &gt;10mm ( Figure ). There was no significant association between either TCV or LCND and PPMI in BE TAVR. Conclusions: PPMI was more common in SE than in BE. The size of LCND was associated an increased risk for SE. The preprocedural assessment of LCND may help the selection of appropriate types of TAVR (SE vs. BE) to reduce the risk for PPMI.
Abstract 14490: Relationship Between Right Heart Catheterization Hemodynamics and Glycosylated Hemoglobin Levels in Adults With Heart Failure With Reduced Ejection Fraction
Authors: Gaspar Del Rio-Pertuz, Cristina Morataya, Kanak Parmar, Zeyad Elharabi, Daniel Davis, Mostafa Abohelwa, Ozman Ochoa, Alison Tran, Kenneth Nugent, Erwin E Argueta-Sosa
Journal: Circulation (2022)

Introduction: Elevated glycosylated hemoglobin (HbA1c) levels have been associated with adverse outcomes in heart failure (HF). However, the relationship between hemodynamics and glycemia has not been established. Hypothesis: Elevated HbA1c levels are associated with abnormal right heart catheterization (RHC) hemodynamic parameters in patients with HF with reduced ejection fraction and no prior diagnosis of diabetes mellitus (DM). Methods: We performed a retrospective study of adults patients (&gt;21 years) with a left ventricular ejection fraction &lt;40% who underwent a RHC between June 1, 2015 and June 1, 2021 and had HbA1c levels measured 30 days before or after the RHC. We excluded patients who had received blood transfusions within 90 days prior to HbA1c measurement and patients with known DM. We conducted univariate and multivariate regression analysis adjusted for age, gender, and body mass index (BMI) to test for an association between RHC hemodynamic parameters and HbA1c. Results: A total of 136 patients were included with a mean age of 55 ± 15 years; 75% were males. The mean BMI was 29.88 ± 8.08 kg/m2, and meanHbA1c was 5.99 ± 0.64%. Unadjusted univariate models showed that HbA1c is significantly associated with cardiac index (CI) by Fick and thermodilution, right atrial pressure (RAP), and mean pulmonary arterial pressure (mPAP). After multivariateanalysis, for every one unit increase in HbA1c, there was a 0.19 and 0.26 L/min/m2decrease in expected CI by thermodilution and by Fick, respectively ( P = 0.03 and P &lt;0.01). For every one unit increase in HbA1c, there was a 2.39 mmHg increase in expected RAP ( P = 0.01). There was no association between MPAP and HbA1c after adjustment (Table 1). Conclusions: Changes in HbA1c levels measured within 30 days before or after the index RHC in patients with a left ventricular ejection fraction &lt;40% were associated withchanges in hemodynamic parameters that correlate with congestive hemodynamics(reduced CI and elevated RAP).
Abstract 14927: Real-Time Super-Resolution Analysis of Sarcomere Motion Reveals Context-Dependent Stochastic Heterogeneity in Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Daniel Haertter, Lara Hauke, Christoph F Schmidt, Wolfram H Zimmermann
Journal: Circulation (2022)

Studies of sarcomere dynamics in cardiac myofibrils are key to understand how myosin-actin contractility translates to whole heart contractions. Such analyses require high spatial (nm) and temporal (ms) resolution of multiple sarcomeres in parallel. Here, we present a new imaging and computational method to analyze sarcomere structure and function in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes. For this we (1) engineered a fluorescent z-band tag (ACTN2-Citrine) by CRISPR-editing, (2) developed micropatterned soft (7:1, 10 kPa) substrate cultures to mimic in vivo conditions, (3) made use of high-speed microscopy (66 fps), and (4) designed an automated AI-based sarcomere detection and analysis tool (SarcAsM - Sarcomere Analysis Multitool). Cardiomyocytes were differentiated from the ACTN2-Citrine iPSC-line and purified using a staged growth factor and metabolic selection protocol (&gt;95% purity with a ventricular myocyte phenotype). Our analysis revealed highly heterogeneous single sarcomere motion, i.e., shortening and lengthening patterns during the same time of the contraction cycle. Notably, the observed rich dynamics on single sarcomere-level are not apparent from whole cell analyses. Interestingly, culture on stiffer substrates (&gt;20 kPa; mimicking cardiac fibrosis) resulted in reduced cell-level contraction, but constant sarcomere level contractility with however enhanced heterogeneity. Analysis of a large data set (&gt;1,200 cells) in conjunction with a biophysical model showed that heterogeneous sarcomere motion is not caused by static non-uniformity (e.g., strong/weak sarcomeres), but can be primarily attributed to the stochastic and non-linear nature of sarcomere dynamics and thus occurs intrinsically during cardiomyocyte beating. Our findings show that that sarcomere heterogeneity is an important feature of cardiomyocyte contractility. The introduced tools for unbiased high-throughput analysis of sarcomere-level dynamics can be exploited to gain a better understanding on how sarcomere level contractility translates to whole cardiomyocyte contractions under simulated physiological and pathological conditions.
Abstract 14608: QRS Voltage in Lead V1 After Cardiac Resynchronization Predicts Survival in Patients With Left Bundle Branch Block
Authors: Iulia G Zehan, Csilla A Eotvos, Giorgia Coseriu, Mihai Andrei, Calina P Schiop-Tentea, Adriana Porca, Dan Blendea
Journal: Circulation (2022)

Introduction: The QRS complex on the electrocardiogram is a reflection of the summation of instantaneous electrical forces within the heart. In left bundle branch block (LBBB), the propagation of the electrical wavefront is dyssynchronous and unopposed and is thereby associated with an increase in the QRS voltage in precordial leads like lead V1, which are closer to perpendicular to the direction of propagation. Hypothesis: The aim of this study was to assess the impact of cardiac resynchronization therapy (CRT) on QRS morphology and voltage in lead V1, and its ability to predict response. Methods: The study included 103 consecutive patients with LBBB (age 69±12 years, 80 men, left ventricular ejection fraction 22±6%, QRS width 159±22ms), who received CRT for a median duration of 42 months (IQR 28-53 months). Results: During follow-up 18 patients died. Total QRS amplitude in lead V1 decreased significantly from 1.4±0.9mV at baseline to 0.8±0.5mV post CRT, (P value = 0.0002), the decrease being more pronounced in patients who survived when compared to nonsurvivors (0.8±0.9mV vs. 0.3±0.9mV P value= 0.021). The algebric sum of the positive and negative deflections of the QRS complex in V1 (sumQRS V1 ) changed significantly from -1.4±0.7mV at baseline to -0.05±0.7mV post CRT (p value &lt;0.0001). Patients who survived had a more negative sumQRS V1 post CRT than nonsurvivors (-0.2±0.6mV vs +0.4±0.5mV p value=0.0012), and the sumQRS V1 cutoff that best separated survivors from non-survivors was +0.3mV. Patients with sumQRS V1 &lt; 0.3mV had a significantly better survival than patients with sumQRS V1 ≥0.3mV (Figure). A &gt;50% decrease in QRS amplitude in V1 with CRT, and sumQRS V1 post CRT &lt;0.3mV independently predicted event free survival in a multivariate Cox regression model that included age, gender, baseline left ventricular ejection fraction and the change in QRS duration. Conclusions: Changes in QRS voltage in lead V1 after CRT predict survival in patients with LBBB.
Abstract 15140: Post-Myocardial Infarction Ventricular Septal Defect in a Patient With Mixed Connective Tissue Disorder
Authors: Adam Gardy, Gian Lima, Jarred Sargeant
Journal: Circulation (2022)

Mixed connective tissue disorder (MCTD) is associated with a broad range of cardiovascular abnormalities, including coronary artery disease (CAD). It has been proposed that chronic systemic inflammation plays a key role in the development of atherosclerotic disease. A 66-year-old female with a history of MCTD and hypertension presented with mild dyspnea and pleuritic chest pain after one week of persistent flu-like symptoms. Her blood pressure was 108/77 mmHg, pulse 92 bpm, saturating 98% on room air. She was comfortable and denied other risk factors such as diabetes, hyperlipidemia, or prior smoking history. On exam she was found to have a soft holosystolic murmur across her precordium. EKG showed sinus rhythm with small Q waves and ST elevation in V1-V6. She was taken for cardiac catheterization which revealed a thrombotic occlusion in the proximal left anterior descending artery (LAD) and a severe lesion in the left circumflex artery. She underwent angioplasty with one drug eluted stent placed to LAD. Left ventriculography revealed a VSD near the apex, and transthoracic echocardiogram showed a 7.6 mm muscular VSD with left to right shunt, ejection fraction of 35% and hypokinesis of the anterior wall. She became hypotensive and required vasopressors prior to coronary artery bypass grafting and primary closure of her apical VSD. Intraoperatively, a 2 cm VSD with 5 cm of necrotic surrounding tissue was noted. Post-operative complications included asystolic cardiac arrest, marked cardiogenic shock and multiorgan failure to which she ultimately succumbed. Post-myocardial infarction VSD is a rare complication of MI occurring in approximately 0.2% of cases. However, patients with MCTD can develop atypical symptoms, resulting in delayed presentation and therefore higher risk of mechanical complications. We highlight the importance of a thorough physical exam and high suspicion for mechanical complications in these patients even when hemodynamically stable.
Abstract 14971: Loss of ZBTB46 Decreases BCL2A Expression and Increases Endothelial Cell Apoptosis
Authors: Holly C Williams, Yu Wang, Amir Rezvan
Journal: Circulation (2022)

Introduction: Endothelial cell (EC) activation, injury, and apoptosis in areas of the vasculature experiencing low and oscillatory shear stress (or disturbed flow) play a key role in the development and pathogenesis of atherosclerosis. In in vivo and in vitro studies, we have demonstrated that ZBTB46, a member of the BTB-ZF protein family of transcription factors, is down-regulated in ECs exposed to disturbed flow when compared to cells experiencing unidirectional laminar shear stress. Additionally, we have observed that germline deletion of ZBTB46 leads to decreased BCL2A expression in mouse carotid arteries. Given that ZBTB46 down-regulation occurs in areas of the vasculature prone to increased EC apoptosis and loss of ZBTB46 in vivo is associated with down regulation of anti-apoptotic protein BCL2A, we explored the role of ZBTB46 in EC apoptosis. Hypothesis: Loss of ZBTB46 negatively regulates transcription of the anti-apoptotic mediator BCL2A and sensitizes EC to apoptosis. Methods: Human aortic endothelial cells (HAEC) were transfected with either ZBTB46-siRNA or control siRNA, grown to 2 days post-confluence to induce ZBTB46 expression and then harvested for RNA. Gene expression was assessed by quantitative real-time PCR. In assays to measure apoptosis, siZBTB46 transfected cells, and corresponding controls were treated with various concentrations (0-400 micro molar) of hydrogen peroxide (H 2 O 2 ) for 18 hours, stained for Annexin V and imaged by confocal microscopy Results: Down regulation of ZBTB46 using siRNA (siZBTB46) in HAEC led to a 78% ± 9% (SEM) reduction in BCL2A1 mRNA expression (n=4, p=0.004) when compared to controls (siCtrl). BCL2A1 downregulation also coincided with increased apoptosis in ZBTB46 deficient HAEC (siZBTB46 39% ± 2.9% v siCtrl 27% ± 3.5% n=6, p=0.026) as measured by Annexin V staining. Additionally, H 2 O 2 -induced apoptosis was exacerbated by loss of ZBTB46 in HAEC at 100 μM (siZBTB46 68% ± 2.1% v siCtrl 30% ± 3.1% n=5-6, p=0.001), 200 μM (siZBTB46 82% ± 1.2% v siCtrl 44% ± 3.2% n=4-5, p=0.001), and 400 μM H 2 O 2 (siZBTB46 88% ± 1.1% v siCtrl 58% ± 5.6% n=5-6, p=0.001). Conclusions: Loss of ZBTB46 in endothelial cells reduces BCL2A expression and increases the susceptibility of endothelial cells to apoptosis.
Abstract 15133: Matricellular Protein CCN1 Regulates Cardiac Fibroblast ECM Synthesis and Alignment
Authors: Annalara G Fischer, Andrea R Poole, Erin M Elliott, Joseph B Moore
Journal: Circulation (2022)

Introduction: Cellular communication network (CCN) proteins constitute a 6-member family of extracellular matrix (ECM)-associated signaling proteins that have important roles in wound healing and tissue fibrosis. Though their function in the heart is not fully explicated, CCN1 is often indicated as an antifibrotic factor. Yet, CCN1 levels correlate with infarct size and ventricular dysfunction in myocardial infarct patients—signifying a pro-fibrotic role for this factor in the heart. Objective: To determine the contribution of endogenous CCN1 to fibroblast (FB) ECM synthesis and organization. Methods: In vitro murine cardiac FB ECM synthesis, activation, proliferation, and matrix organization was evaluated in cells treated with CCN1 or non-target (NT) siRNA, by qPCR/immunoblotting for collagens and synthetic enzymes, EdU incorporation, and type I collagen immunostaining of decellularized matrices, respectively. CCN1-dependent integrin pathways modulating FB collagen synthetic enzyme expression were identified and interrogated via in vitro immunoprecipitation and RNAi-mediated depletion. Results: CCN1-deficient FBs showed reduced expression of type I collagen and collagen processing enzymes ( P4ha1 , P4hb , Plod1 , Plod2 , Loxl2 ). siRNA-mediated knockdown of CCN1 did not impact FB activation (α-SMA), but significantly reduced the expression of collagen synthetic/processing enzymes ( P4ha1 , Plod1 , Plod2 , Loxl2 ). Deficiency of CCN1 in both unstimulated and TGFβ1-stimulated FBs resulted in reduced proliferative capacity (7.17%, p=0.0205 and 5.34%, p=0.0428, respectively, relative to NT, n=3). CCN1 depletion promoted the alignment of FB-derived collagen fibers (0.30 ± 0.03 vs. 0.58 ± 0.04; mean ± SEM, p&lt;0.0001, n=6). An interaction between CCN1 and integrin αvβ3 was validated; moreover, knockdown of integrin β3 reduced the expression of enzymes associated with collagen cross-linking ( Plod1 , Plod2 , Loxl2 ), partly phenocopying CCN1 depletion. Conclusions: The data suggest that CCN1 drives pro-fibrotic signaling and limits ECM organization in cardiac FBs. This may have implications for CCN1 in the infarcted heart by promoting scar establishment; however, long-term expression could lead to progressive detrimental remodeling.
Abstract 14475: Use of Extracorporeal Membrane Oxygenation in Neonates With Pulmonary Atresia and Intact Ventricular Septum - A Multicenter Study
Authors: Kiona Y Allen, Saul Flores, Rohit Loomba, Christopher Mastropietro, Eva Cheung, Venu Amula, Monique R Radman, David M Kwiatkowski, Bao Puente, Jason Buckley, Karan Karki, saurabh chiwane, katherine Cashen, Kurt Piggott, Yamini Kapileshwarkar, Keshava M Narayana Gowda, Aditya Badheka, Rahul Raman, John M Costello, ilias iliopoulos
Journal: Circulation (2022)

Introduction: Data are limited on use of extracorporeal membrane oxygenation (ECMO) in neonates with pulmonary atresia intact ventricular septum (PAIVS). We aimed to describe ECMO use, risk factors, and associated outcomes in this population. Methods: This is a retrospective analysis of neonates with PAIVS who received ECMO between 2009-2019 in 19 US hospitals affiliated with the Collaborative Research for the Pediatric Cardiac Intensive Care Society (CoRe-PCICS). Patient demographics and clinical, procedural, and imaging data were collected from the medical record. Variables significant on univariate analysis were entered into a logistic regression and a model built to calculate estimated risk of ECMO. A similar analysis compared patients who received ECMO and experienced inpatient mortality to those who did not. A receiver operator curve analysis was conducted to determine the accuracy of this risk score in predicting inpatient mortality. A p-value &lt;0.05 was statistically significant. Results: Of 295 neonates with PAIVS, 32 (11%) were supported with ECMO. By multivariable analyses, a higher left pulmonary artery z-score (OR 2.0; p-value &lt;0.01) and the presence of ventriculocoronary connections by cardiac catheterization (OR 3.4; p-value 0.03) was associated with an increased risk of receiving ECMO. The resulting risk score had an area under the curve of 0.71 for prediction of need for ECMO. Of these 32 ECMO patients, 15 (46%) experienced mortality. By univariate analyses, those who were supported with ECMO, and experienced inpatient mortality had a higher gestational age (p-value 0.04). No significant associations were identified in those supported with ECMO and any independent variable. Conclusions: In a multicenter cohort of patients with pulmonary atresia with intact ventricular septum, 11% received ECMO. Of those supported with ECMO, 46% experienced inpatient mortality. There are risk factors that can help in identifying those who may require ECMO.
Abstract 14939: Changes in Estimated Glomerular Filtration Rate After Retransplantation in Children and Young Adults
Authors: Melvin Chan, Lori Silveira, Daniel J Patterson, Margret E Bock, Bill A Pietra, Melanie D Everitt, KATHLEEN E SIMPSON, Shelley D Miyamoto, Scott R Auerbach
Journal: Circulation (2022)

Introduction: Estimated glomerular filtration rate (eGFR) is abnormal in pediatric heart transplant (HT) patients with graft failure due to hemodynamic compromise and exposure to nephrotoxins. We aimed to evaluate differences in eGFR between primary HT (PT) and repeat HT (RT) in children and young adults. We hypothesized that eGFR will recover to baseline after HT, but RT will tend to have lower eGFR than PT. Methods: We reviewed all HT at our center from 1995-2021. eGFR was derived from the CKid U25 equation. eGFR was measured pre-HT, 1 week post-HT (peak creatinine), 1-3, 6, and 12 months post-HT, and most recent follow-up. We matched PT with RT patients based on age at HT, sex, and race. Changes in eGFR were measured within and between patients using a linear mixed effect model. Additionally, changes in eGFR were stratified between those with pre-HT eGFR &lt; 60mL/min/1.73m2 and &gt;= 60mL/min/1.73m2. We evaluated for associations between changes in eGFR and the number of rejections prior to RT, diagnosis, pre-HT eGFR, dialysis, prior VAD/ECMO support, waitlist time, bypass time, ischemic time, length of stay, time from HT, graft loss, and nephrotoxin exposure. Results: RT was performed in 47 patients (early death N=1). Table 1 shows characteristics of the matched PT (n=36) and RT (n=36) cohort. Figure 1 compares PT and RT mean eGFR at the specified time points. Those with a pre-retransplant eGFR &lt; 60mL/min/1.73m2 rebounded to levels significantly higher than pre-retransplant (p&lt; 0.001). RT eGFR was lower than PT eGFR, but RT eGFR rebounded to levels significantly higher than prior to RT (p&lt;0.001). There were no associations between changes in eGFR and bypass time, ischemic time, length of stay, or graft loss. Conclusions: eGFR falls transiently early after both PT and RT but rebounds back to baseline in PT or above baseline in RT. These findings help to characterize expected changes in renal function after PT and RT and guide expectations for renal recovery afterwards.
Abstract 15820: The Use of Sglt 2 Inhibitors During Hospitalization for Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis
Authors: Fred Henry Daniel Charles, Sri Mandava, Tanesh Ayyalu
Journal: Circulation (2022)

Background: There continues to be emerging data about the benefits of Sodium-glucose co-transporter 2 inhibitor (SGLT2i) in patients with heart failure. This has led to the addition of this medication to guideline-directed medical therapy for heart failure with reduced ejection fraction. There is a discrepancy in whether the use of SGLT2i is beneficial in patients hospitalized for decompensated heart failure. Methods: In this study, a search was completed through PubMed, Scopus, Cochrane Library, ProQuest for randomized controlled trials from 2020 to 2022 that evaluated the impact of the use of SGLT-2 inhibitors (Empagliflozin, Sotagliflozin) in patients admitted with acute HF. After screening for our preset inclusion and exclusion criteria, three randomized controlled clinical trials were eligible for inclusion. We carried out a Meta-analysis of the relative odds on the basis of the random effect model using the Mantel-Haenszel method for the major outcome of the incidence of death from any cause, the number of heart failure events, rehospitalization for heart failure, and time to first heart failure event in the acute setting. Comprehensive Meta-analysis version 3 software was used for analysis. Results: A total of 2,532 patients from the EMPULSE, SOLOIST-WHF, EMPA-RESPONSE-AHF trials were included. After analysis, it was found that the P-value was 0.000, Z-value was -4.103, and the OR 0.508 (95% CI 0.368; 0.702) for the patients on either Empagliflozin or Sotagliflozin. Conclusions: The systematic review and meta-analysis we conducted show that patients who received SGLT-2i (Empagliflozin, Sotagliflozin) during hospitalization within 24 hours or more had a statistically significant decreased odds of all-cause of death, number of heart failure events, and rehospitalization for heart failure.